Inhibition of airway remodeling in IL-5–deficient mice
Jae Youn Cho, Marina Miller, Kwang Je Baek, Ji Won Han, Jyothi Nayar, Sook Young Lee, Kirsti McElwain, Shauna McElwain, Stephanie Friedman, David H. Broide
Jae Youn Cho, Marina Miller, Kwang Je Baek, Ji Won Han, Jyothi Nayar, Sook Young Lee, Kirsti McElwain, Shauna McElwain, Stephanie Friedman, David H. Broide
View: Text | PDF
Article Pulmonology

Inhibition of airway remodeling in IL-5–deficient mice

Abstract

To determine the role of IL-5 in airway remodeling, IL-5–deficient and WT mice were sensitized to OVA and challenged by repetitive administration of OVA for 3 months. IL-5–deficient mice had significantly less peribronchial fibrosis (total lung collagen content, peribronchial collagens III and V) and significantly less peribronchial smooth muscle (thickness of peribronchial smooth muscle layer, α-smooth muscle actin immunostaining) compared with WT mice challenged with OVA. WT mice had a significant increase in the number of peribronchial cells staining positive for major basic protein and TGF-β. In contrast, IL-5–deficient mice had a significant reduction in the number of peribronchial cells staining positive for major basic protein, which was paralleled by a similar reduction in the number of cells staining positive for TGF-β, suggesting that eosinophils are a significant source of TGF-β in the remodeled airway. OVA challenge induced significantly higher levels of airway epithelial αVβ6 integrin expression, as well as significantly higher levels of bioactive lung TGF-β in WT compared with IL-5–deficient mice. Increased airway epithelial expression of αVβ6 integrin may contribute to the increased activation of latent TGF-β. These results suggest an important role for IL-5, eosinophils, αVβ6, and TGF-β in airway remodeling.

Authors

Jae Youn Cho, Marina Miller, Kwang Je Baek, Ji Won Han, Jyothi Nayar, Sook Young Lee, Kirsti McElwain, Shauna McElwain, Stephanie Friedman, David H. Broide

×

Figure 5

Options: View larger image (or click on image) Download as PowerPoint
Lung TGF-β1 in WT and IL-5–deficient mice repetitively challenged with O...
Lung TGF-β1 in WT and IL-5–deficient mice repetitively challenged with OVA. (a) WT mice challenged with OVA developed increased levels of lung TGF-β1 compared with non–OVA-challenged WT mice (*WT OVA versus WT no OVA; P < 0.01). Significantly reduced levels of TGF-β1 were detected in IL-5–deficient mice versus WT mice challenged with OVA (**IL-5 KO OVA versus WT OVA; P < 0.05). (b) WT mice challenged with OVA had a significant increase in the number of peribronchial MBP-positive cells (#WT OVA versus WT no OVA; P < 0.001) and TGF-β–positive cells (†WT OVA versus WT no OVA; P < 0.001). There was a significant reduction in the number of MBP-positive cells (##IL-5 KO OVA versus WT OVA; P < 0.001) and TGF-β–positive cells (††IL-5 KO OVA versus WT OVA; P < 0.001) in IL-5–deficient mice challenged with OVA. (c–j) Non–OVA-challenged WT mice had few cells that immunostained positive for MBP (c) or TGF-β (d). OVA-challenged WT mice had a significant increase in the number of cells that immunostain positive for MBP (e) or TGF-β (f). OVA challenged IL-5–deficient mice had few cells that immunostained positive for MBP (i) or TGF-β (j). Epithelial cells in OVA-challenged IL-5–deficient mice did immunostain positive for TGF-β (j). Non–OVA-challenged IL-5–deficient mice had few cells that immunostained positive for MBP (g) or TGF-β (h). The arrows in k point to three of four MBP-positive cells. The arrows in l point to three cells that are TGF-β1 positive (corresponding to the same three MBP-positive cells in k). Several additional TGF-β1–positive cells that do not correspond to MBP-positive cells are also noted in l.